Synthesis and spectroscopic studies of diorganotin derivatives with tolfenamic acid. Crystal and molecular structure of the first complex of tolfenamic acid, 1,2:3,4-di-μ 2-2-[(3-chloro-2-methylphenyl)amino]-benzoato-O,O-1,3-bis-2-[(3- chloro-2-methylphenyl)amino]benzoato-O-1,2,4:2,3,4-di-μ 3-oxo-tetrakis[di-n-butyltin(IV)]

Article abstract of DOI:10.1016/S0022-328X(00)00819-6

The complexes [Me₂LSnOSnLMe₂]₂ (1) [Bu₂LSnOSnLBu₂]₂ (2) and Bu₂SnL₂.H₂O (3), where HL is 2-[bis(3-chloro-2-methylphenyl)amino]benzoic acid (tolfenamic acid), have been prepared and characterized structurally by means of ¹⁹Sn M?ssbauer, vibrational and ¹H- and ¹³C-NMR spectroscopies. The crystal structure of complex 2 has been determined by X-ray crystallography. Three distannoxane rings are present to the dimeric tetraorganodistannoxanes of planar ladder arrangement with distorted trigonal-bipyramidal geometry about the five-coordinated tin centers. The structure, which has twofold symmetry, features a central Sn₂O₂ unit with two additional tin atoms linked at O. Pairs of tin atoms are bridged by bidentate carboxylate ligands and the external tin atoms have their coordination geometry completed by a monodentate carboxylate ligand. The tin atom geometries are similar and are based on a trigonal bipyramidal arrangement. Significant π → π stacking, C-H-π interactions and intrarmolecular hydrogen bonds stabilize this structure. The polar imino hydrogen atom on N(1) and N(2) participate in a bifurcate intramolecular hydrogen bond. In this case complex 2 is self-assembled via C-H-π and π → π stacking interactions. Tin-119 M?ssbauer, vibrational and NMR data are discussed in terms of the crystal structure and the proposed structures for 1 and 3. From the variable-temperature M?ssbauer effect, the Debye temperatures for 1-3 were determined.

Full text of DOI:10.1016/S0022-328X(00)00819-6

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 620 (2001) 194–201
Synthesis and spectroscopic studies of diorganotin derivatives with
tolfenamic acid. Crystal and molecular structure of the first
complex of tolfenamic acid, 1,2:3,4-di-m2-2-[(3-chloro-2-
methylphenyl)amino]-benzoato-O,O-1,3-bis-2-[(3-chloro-
2-methylphenyl)amino]benzoato-O-1,2,4:2,3,4-di-
m3-oxo-tetrakis[di-n-butyltin(IV)]
Dimitra Kovala-Demertzi a,*, Nikolaos Kourkoumelis a, Aglaia Koutsodimou b,
Alice Moukarika c, Ernst Horn d,e, Edward R.T. Tiekink f
a Department of Chemistry, Inorganic Chemistry, Uni6ersity of Ioannina, 45110 Ioannina, Greece
b NRPCS Democritos, Institute of Physical Chemistry, 15310 Aghia paraske6i Attikis, Greece
c Department of Physics, Uni6ersity of Ioannina, 45110 Ioannina, Greece
d Department of Chemistry, Rikkyo Uni6ersity, Nishi-Ikebukuro, Tokyo 171-8501, Japan
e Tsukuba Ad6anced Research Alliance, Uni6ersity of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan
f Department of Chemistry, The Uni6ersity of Adelaide, Adelaide 5005, Australia
Received 5 September 2000; received in revised form 7 October 2000; accepted 7 October 2000
Abstract
The complexes [Me2LSnOSnLMe2]2 (1) [Bu2LSnOSnLBu2]2 (2) and Bu2SnL2.H2O (3), where HL is 2-[bis(3-chloro-2-
methylphenyl)amino]benzoic acid (tolfenamic acid), have been prepared and characterized structurally by means of 19Sn
1
Mo¨ssbauer, vibrational and H- and 13C-NMR spectroscopies. The crystal structure of complex 2 has been determined by X-ray
crystallography. Three distannoxane rings are present to the dimeric tetraorganodistannoxanes of planar ladder arrangement with
distorted trigonal-bipyramidal geometry about the five-coordinated tin centers. The structure, which has twofold symmetry,
features a central Sn2O2 unit with two additional tin atoms linked at O. Pairs of tin atoms are bridged by bidentate carboxylate
ligands and the external tin atoms have their coordination geometry completed by a monodentate carboxylate ligand. The tin
atom geometries are similar and are based on a trigonal bipyramidal arrangement. Significant p“p stacking, C–H–p interactions
and intrarmolecular hydrogen bonds stabilize this structure. The polar imino hydrogen atom on N(1) and N(2) participate in a
bifurcate intramolecular hydrogen bond. In this case complex 2 is self-assembled via C–H–p and p“p stacking interactions.
Tin-119 Mo¨ssbauer, vibrational and NMR data are discussed in terms of the crystal structure and the proposed structures for 1
and 3. From the variable-temperature Mo¨ssbauer effect, the Debye temperatures for 1–3 were determined. © 2001 Elsevier
Science B.V. All rights reserved.
Keywords: Tin; Tolfenamic acid; Organotin; Mo¨ssbauer
anthranilic acid) (Scheme 1) is a potent, well-tolerated
non-steroidal anti-inflammatory drug (NSAID) with a
1. Introduction
low gastroulcerogenicity [1], a low overall toxicity and
high therapeutic indices. It possesses analgesic and an-
tipyretic properties as demonstrated in several animal
models and has shown good results in long-term treat-
Tolfenamic acid (i.e. 2-[bis(3-chloro-2-methylphenyl)-
amino]benzoic acid or N-(3-chloro-2-methylphenyl)-
ment of rheumatoid arthritis and osteoarthritis [2].
* Corresponding author.
Chemically, it resembles mefenamic and flufenamic
E-mail address: dkovala@cc.uoi.gr (D. Kovala-Demertzi).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(00)00819-6

D. Ko6ala-Demertzi et al. / Journal of Organometallic Chemistry 620 (2001) 194–201
195
acids, other fenamates in clinical use. Tolfenamic acid
2. Experimental
inhibits the biosynthesis of prostagladins and has an
inhibitory action on prostagladin receptors. Inhibitory
effects on the biosynthesis of leukotrienes in vitro and
ex vivo have been demonstrated [3]. X-ray crystal struc-
ture investigations of tolfenamic acid revealed the exis-
tence of two polymorphic forms containing the
molecule as different conformers [4]. The poor water
solubility of tolfenamic acid is the main difficulty in its
pharmaceutical formulation and complexation with
various cyclodextrins has been tried in order to circum-
vent bioavailability problems [5].
Organotin(IV) carboxylates form an important class
of compounds and have been receiving increasing atten-
tion in recent years, not only because of their intrinsic
interest but owing to their varied applications. Some
examples find wide use as catalysts and stabilizers, and
certain derivatives are used as biocides, as antifouling
agents and as wood preservatives [6]. In recent years,
investigations have been carried out to test their anti-
tumour activity and it has been observed that indeed
several diorganotin species, as well as triorganotin spe-
cies, show potential as antineoplastic agents [7]. The
mechanism of their activity may involve the transporta-
tion of the complexed organotin compound into the
tumor cells, followed by reaction of uncomplexed
organotin and its hydrolysis products at the active sites.
This suggestion is supported by the fact that their
hydrolysis products are active.
2.1. General and instrumental
The reagents (Aldrich, Merck) were used as supplied
while the solvents were purified according to standard
procedures. Tolfenamic acid was a gift from ‘ELPEN
A.E’. C, H, and N analyses were carried out by the
microanalytical service of the University of Ioannina.
Melting points were determined in open capillaries and
are uncorrected. Infrared and far-infrared spectra were
recorded on a Nicolet 55XC Fourier transform spec-
trophotometer using KBr pellets (4000–400 cm−1) and
nujol mulls dispersed between polyethylene disks (400–
1
40 cm−1). The H (250.13 MHz), 13C (62.90 MHz), 2D
1H–1H shift correlated spectra (COSY), 2D 13C–1H
shift correlated spectra (HETCOR) and 2D long range
13C–1H shift correlated spectra (COLOC) NMR spec-
tra were recorded on a Bruker AC-250E spectrometer
equipped with an Aspect 3000 computer (using DISNMR
program, version 1991) and a 5 mm 13C/1H dual probe
head (1H 90° pulse width=10.2 ms, 13C 90° pulse
width=10.4 ms). Samples were dissolved in CDCl3 or
DMSO-d6 and spectra were obtained at room tempera-
ture with the signal of the free DMSO or CHCl3 (at
2.49 and 7.24 ppm, respectively) as a reference. Mo¨ss-
bauer measurements were carried out using a constant-
acceleration Mo¨ssbauer spectrometer with a Ba119SnO3
source maintained at room temperature. A Pd filter was
used to eliminate the 25.8 keV×radiation. A variable-
temperature liquid-nitrogen cryostat (Oxford Instru-
ments) was used for the low temperature measurements.
Suitable computer programs have been employed in the
fitting procedure of the experimental spectra using
Lorentzian line shapes. The estimated errors are 90.02
mm s−1 for the hyperfine parameters and 93% for the
spectral areas.
Given the pharmacological importance of tolfenamic
acid and the potential biological activity of organotin
carboxylates, it was thought of some interest to explore
the chemistry of organotin/tolfenamic acid compounds.
As a continuation of our studies of biological organotin
chemistry [8] and on the coordination chemistry and
anti-inflammatory properties of non-steroidal anti-infl-
ammatory drugs [9], we report here the synthesis and
spectral characterization of [R2LSnOSnLR2]2 (where
R=CH3 (1), Bu (2) and L is deprotonated tolfenamic
acid) and Bu2SnL2·H2O (3). The complexes have been
structurally characterized in the solid state by means of
temperature-dependent 119Sn Mo¨ssbauer spectroscopy
which allowed the determination of lattice dynamics.
2.2. Synthesis
2.2.1. [Me2LSnOSnLMe2]2 (1)
To a solution of di-methyl oxide (0.198 g, 1.2 mmol)
in benzene (20 ml) was added a solution of tolfenamic
acid (0.262 g, 1 mmol) in benzene (10 ml). The reaction
mixture was refluxed for 3 h with azeotropic removal of
water via a Dean–Stark trap. The resulting clear solu-
tion was rotary evaporated under vacuum to a small
volume, chilled and triturated with diethylether to give
a white solid; m.p. 190–192°C. Yield 52%. Anal.
Found: C, 45.97; H, 3.88; N, 3.18. Calc.: C, 46.04; H,
4.10; N, 3.36%.
1
Vibrational and H- and 13C-NMR spectroscopic stud-
ies, and the crystal and molecular structure of 2 is also
described.
2.2.2. [Bu2LSnOSnLBu2]2 (2)
Di-n-butyl oxide (0.373 g, 1.5 mmol) and tolfenamic
acid (0.366 g, 1.4 mmol) and 70 ml of benzene were
refluxed overnight with azeotropic removal of water via
Scheme 1.

196
D. Ko6ala-Demertzi et al. / Journal of Organometallic Chemistry 620 (2001) 194–201
Fig. 1. Perspective view of [Bu2SnLOLSnBu2]2 (2) showing the atomic numbering scheme.
a Dean–Stark trap. The resulting clear solution was
rotary evaporated under vacuum to a small volume.
Drops of diethylether were added and after slow evapo-
ration, white crystals were grown. m.p. 99–100°C.
Yield 58%. Anal. Found: C, 52.39; H, 5.71; N, 2.78.
Calc.: C, 52.68; H, 5.82; N, 2.79%.
was found to be disordered over two positions. Refine-
ment showed occupancy ratio 0.67:0.33; H atoms were
not included for this group.
3. Results and discussion
2.2.3. Bu2SnL2·H2O (3)
3.1. Crystal structure of 2
Di-n-butyl oxide (0.373 g, 1.5 mmol) and tolfenamic
acid (0.785 g, 3 mmol) and 80 ml of benzene were
refluxed overnight with azeotropic removal of water via
a Dean–Stark trap. The resulting clear solution was
rotary evaporated under vacuum to a small volume,
chilled and triturated with diethylether to give a white
oil which solidified after 1–2 days in vacuum. The
product was washed with acetone and filtered to give a
white solid; m.p.: 86–87°C. Yield 55%. Anal. Found:
C, 55.24; H, 5.83; N, 3.46. Calc.: C, 55.99; H, 5.48; N,
3.63%.
Compound 2 is obtained by azeotropic removal of
water from the reaction between the di-n-butyl oxide
and tolfenamic acid in the molar ratio 1:1 conducted in
benzene. The molecular structure is shown in Fig. 1 and
selected interatomic parameters are collected in Table 1.
Compound 2 is a centrosymmetric dimer built up
around the planar cyclic Sn2O2 unit. The two oxygen
atoms of this unit are tridentate as they link three Sn
centres, two endo-cyclic and one exo-cyclic. Additional
links between the endo- and exo-cyclic Sn atoms are
provided by bidentate carboxylate ligands that form
,
2.3. X-ray crystallography [10]
essentially symmetrical bridges (Sn(1)–O(2) 2.241(4) A
,
and Sn(2)–O(3) 2.315(4) A). Each exocyclic Sn atom is
C88H116Cl4N4O10Sn4, M=2006.5, triclinc, a=
also coordinated by a monodentate carboxylate ligand
,
,
12.223(2), b=19.643(3), c=11.294(2) A, h=105.13(1),
(Sn(2)–O(4) 2.181(3) A). The overall geometry found in
the structure, allowing for differences in chemistry, is
similar to that found in the common motif adopted by
3
,
i=116.59(1), k=92.24(2)°, V=2302.2(9) A , Z=1
(tetramer), T=253 K, v(Mo–Ka)=12.44 cm−1
,
13830 reflections measured on a Rigaku AFC7R dif-
fractometer, qmax 30.0°, 13247 unique (Rint=0.042),
8065 with I]3.0|(I) were used in subsequent calcula-
tions: final R=0.045 and Rw=0.068. One butyl chain
compounds
with
the
general
formula
[R2(R%CO2)SnOSn(O2CR%)R2]2 [11]. To a first approxi-
mation, the coordination geometry about each of the
Sn atoms is best described as distorted trigonal bipyra-

D. Ko6ala-Demertzi et al. / Journal of Organometallic Chemistry 620 (2001) 194–201
197
Table 1
cant bonding interactions between Sn and O, they do
exert an influence on the respective coordination ge-
ometries as seen in the expansion of the C–Sn–C
angles to 142.6(2) and 132.6(2)° [145.6(3)° for the minor
component of the disordered C(61)–C(64) butyl group]
for Sn(1) and Sn(2), respectively. The aminobenzoate
portion of each carboxylate ligand is effectively planar
presumably so as to facilitate the formation of in-
tramolecular N(1)–H···O(3) and N(2)–H···O(5) interac-
a
,
Selected bond lengths (A) and bond angles (°) for 2
Bond lengths
Sn(1)–O(1)
Sn(1)–O(1)i
Sn(1)–O(2)
Sn(1)–C(31)
Sn(1)–C(41)
2.037(2)
2.178(2)
2.242(2)
2.128(3)
2.124(3)
Sn(2)–O(1)
Sn(2)–O(3)
Sn(2)–O(4)
Sn(2)–C(51)
Sn(2)–C(61)
2.035(3)
2.316(3)
2.181(3)
2.141(3)
2. 11(1)
[2.24(2)]
Bond angles
,
tions of 1.91 and 1.88 A, respectively. By contrast,
O(1)–Sn(1)–O(1)
O(1)–Sn(1)–O(2)
O(1)–Sn(1)–C(31)
O(1)–Sn(1)–C(41)
76.6(1)
91.6(1)
109.1(2)
108.0(2)
O(1)–Sn(2)–O(3)
O(1)–Sn(2)–O(4)
O(1)–Sn(2)–C(51)
O(1)–Sn(2)–C(61)
88.7(1)
80.7(1)
significant twists between the aromatic fragments of
bidentate and monodentate ligands are noted. The di-
hedral angles between the aminobenzoate aromatic ring
and the other ring are 78.0(3) and 47.8(2)°, respectively.
Remarkably, these are comparable to the angles of 73
and 46°, respectively, found in the two white and yellow
forms of free tolfenamic acid.
111.4(2)
112.6(2)
[102.9(3)]
168.8(1)
83.2(2)
81.0(2)
[95.32(3)]
97.5(2)
O(1)i–Sn(1)–O(2)
O(1)i–Sn(1)–C(31)
O(1)i–Sn(1)–C(41)
167.0(1)
94.7(2)
97.8(2)
O(3)–Sn(2)–O(4)
O(3)–Sn(2)–C(51)
O(3)–Sn(2)–C(61)
O(2)–Sn(1)–C(31)
O(2)–Sn(1)–C(41)
84.0(2)
91.0(2)
O(4)–Sn(2)–C(51)
O(4)–Sn(2)–C(61)
The unit cell of 2 comprises one centrosymmetric,
dimeric distannoxane molecule. Translationally related
(along a) molecules associate via p–p stacking interac-
tions so that slightly displaced C(2)–C(7) and C(16)–
C(21) rings face each other. The average separation
106.0(2)
[90.3(3)]
C(31)–Sn(1)–C(41) 142.6(2)
C(51)–Sn(2)–C(61) 132.6(2)
[145.6(3)]
Sn(1)–O(1)–Sn(1)i
Sn(1)–O(1)–Sn(2)i
Sn(2)–O(3)–C(1)
103.4(1)
120.4(1)
133.4(2)
Sn(1)–O(1)–Sn(2)
Sn(1)–O(2)–C(1)
Sn(2)–O(4)–C(15)
135.9(2)
135.5(3)
106.7(2)
,
between the two rings is 3.56 A (dihedral angle 5.6°),
,
however, the closest separation of 3.522(8) A occurs
between the C(3) and C(19) atoms. Evidence for a
C–H···p interaction is also found in the structure. The
C(24)–H atom is directed towards the symmetry re-
lated (−1−x, −1−y, −z) aromatic ring containing
the C(8)–C(13) atoms but in particular towards the
C(10)–C(12) atoms of this ring. The closest contact of
a Symmetry operation i: −x, −y, 1−z; parameters given in square
brackets are for the minor component of the disordered C(61)–C(64)
butyl group.
midal with axial positions occupied by O atoms. Distor-
tions from the ideal geometry arise, in part, owing to
,
the close intramolecular approach of O atoms such that
2.78 A occurs between the H and C(11) atoms. Further,
i
,
Sn(1)···O(4) is 2.818(2) A and Sn(2)···O(5) is 2.729(3)
intramolecular hydrogen bonds stabilize this structure.
The polar imino hydrogen atom on N(1) and N(2)
participate in a bifurcate intramolecular hydrogen
,
A; symmetry operation i: −x, −y, 1−z. While these
separations are considered too long to represent signifi-
Table 2
C–H-p, p–p and intra-hydrogen bonds for 2
H···Cg
3.200
3.081
3.058
C···Cg
3.581
3.910
3.526
C–H···Cg
105.35
133.88
C(42)–H(42B)“Cg(1)i
C(24)–H(24)“Cg(4)ii
C(32)–H(32)“Cg(1)i
111.12
a
c
Cg(I)“Cg(J)
Cg(3)“Cg(5)iii
Cg(5)“Cg(3)i6
Cg–Cg b
3.779
3.786
i
CgI-Perp d
3.570
3.439
CgJ-Perp e
3.439
3.570
19.13
24.93
D
H
A f
D···A
H···A
D–H···A
131.71
134.23
104.85
106.54
N(1)
N(2)
C(14)
C(28)
H(1)
H(2)
H(14)
H(28)
O(3)
O(5)
N(1)
N(2)
2.635(5)
2.631(5)
2.839(8)
2.860(4)
1.9490
1.8781
2.3638
2.3588
a Where Cg(1), Cg(3), Cg(4) and Cg(5) are referred to the centroids Sn1–O1–Sn1a–O1a, C3–C4–C5–C6–C7, C8–C9–C10–C11–C12–C13, and
C16–C17–C18–C19–C20–C21, respectively.
b Cg–Cg is the distance between ring centroids; symmetry transformations: i, −x, −y, 1−z; ii, −1−x, −1−y, −z; iii, 1+x, y, z; and i6,
−1+x, y, z.
c Where i is the angle Cg(I)“Cg(J) or Cg(i)“Me vector and normal to plane I (°).
d CgI-Perp is the perpendicular distance of Cg(I) on ring J
e CgJ-Perp is the perpendicular distance of Cg(J) on ring I.
f D, donor; A, Acceptor.

198
D. Ko6ala-Demertzi et al. / Journal of Organometallic Chemistry 620 (2001) 194–201
Fig. 2. Packing diagram of the complex [Bu2SnLOLSnBu2]2 viewed along the h.
bond, Table 2. In this case complex 2 is self-assembled
via C–H–p and p“p stacking interactions and a
different packing arrangement from bis(2-[(2,6-
dichlorophenyl)amino]phenyl]acetate) oxide results [7f].
A view of the crystal packing along the h axis is shown
in Fig. 2.
3.2.2. NMR spectra
The 1H- and 13C-NMR data for tolfenamic acid,
Scheme 1 and 1–3 are summarized in Table 3. The lack
of published information on tolfenamic acid made it
necessary to perform 1H (250.13 MHz), 13C (62.90
1
MHz), 2D H–1H shift correlated spectra (COSY), 2D
13C–1H shift correlated spectra (HETCOR) and 2D
long range 13C–1H shift correlated spectra (COLOC)
NMR spectra in order to completely assign the reso-
nances in the tolfenamic acid and 1–3. Involvement of
the carboxyl group in bonding to Sn is confirmed by
the resonance ascribed to C1, which either disappears
or exhibits the greatest shift upon coordination. The
3.2. Spectroscopy
3.2.1. Infrared spectroscopy
The IR of the diorganotins, 1, 2 and 3 gave bands at
w 3340 and 3290 cm−1 attributable to intramolecular
NH···O hydrogen bonds. The was(COO) and wsym(COO)
bands appear at w 1615, 1580 cm−1 and w 1450 and
1370 cm−1, respectively, for 1 and 2, and appear at w
1662 and 1374 cm−1 for 3. The difference between
these bands for 1 and 2, D [D=was(COO)−wsym(COO)],
is close to that found for a unidentate carboxylate
ligand (ca. 215 cm−1) and a bidentate bridging car-
boxylate (ca. 170 cm−1), respectively [8,12]. The differ-
ence between these two bands for 3, i.e. 288 cm−1, is
close to that observed for asymmetric bidentate chelate
1
existence of the NH resonance in the H-NMR spectra
indicates that the nitrogen atom remains protonated in
1–3. The small downfield shift of the NH resonance in
CDCl3 solution suggests that no significant participa-
tion in intermolecular hydrogen-bonding takes place.
The remaining resonances due to the aromatic car-
bon atoms for 1 do not shift considerably after binding
to Sn, with C3% exhibiting the greatest upfield shift (1.3
ppm). No resonance attributable to the carbonyl C
nucleus was found, behaviour that has been noted
previously for related systems [13]. Three resonances
attributed to the tin-bound methyl carbons are found, a
result that is consistent with the presence of a dimer in
solution by analogy with related compounds [14]. In the
1H-NMR spectrum of 1, three singlets appear in the
mode [12]. Two bands at 490–480 and 446–427 cm−1
,
for 1 and 2, are assigned to was,sym(SnO)2, indicating
non-linear Sn–O moieties, while the bands at 230–
190 cm−1 are assigned to the tin–oxygen (COO)
bridging and unidentate stretching modes, respectively
[8,12].

Table 3
Proton and 13C-NMR data
OH
NH
H3
H4
H5
H6
H4%
H5%
H6%
CH3
a
Tolf
13.12
9.57
7.91dd,
6.76td,
7.35td,
6.81dd,
7.28d 7.22
7.20d 2.24s
J(3–4)=7.8,
J(3–5)=1.8
8.01dd,
J(3–4)=7.7,
J(3–5)=1.7
8.10br
J(4–6)=0.9
J(4–5)=8.3
J(6–5)=8.3
Tolf b
1 b
9.15
6.73t,
J(4–6)=0.8
7.31td,
J(4–5)=8.1
6.75d,
J(6–5)=8.5
7.25d 7.12t,
7.25d 2.32s
J(5%–4%)=7.7,
J(5%–6%)=7.7
7.31d 7.11t,
J(5%–4%)=7.7,
J(5%–6%)=7.7
7.20d 7.11t,
Me2Sn,
9.43br
9.52s/9.27
6.61br
6.57t
7.17td,
J(4–5)=8.2
6.84d,
J(6–5)=8.2
7.31d 2.32s
0.99s/1.07s,
1.15s/1.15s
Bu2Sn,
Hd:0.90, Hg:
0.76; Hb: 1.66,
Ha: 1.29
Bu2Sn, Hd:
0.89; Hg: 1.41;
Ha, b: 1.77
/
2 b
8.12d/7.88d,
J(3–4)=7.7
7.27t,
J(4–5)=8.2
6.90d/6.80d,
J(6–5)=8.8
7.20d 2.33s/2.31s
J(5%–4%)=7.7
J(5%–6%)=7.7
3 b
9.28s
C1
8.13d,
J(3–4)=7.7
6.76t
C3
7.13t
6.90d,
J(6–5)=8.3
7.30d 7.17t,
7.30d 2.34s
J(5%–4%)=7.7,
J(5%–6%)=7.7
COOH
C2
C4
C5
C6
C1%
C2%
C3%
C4%
C5%
C6%
Me
Tolf. a 170.1
112.2
109.9
147.5
149.4
148.4
131.8
132.5
131.2
117.3
117.0
117.0
134.2
135.3
135.6
113.6 140.5
113.8 140.1
113.8 140.7
129.8 134.4
132.2 135.7
132.3 133.8
122.1 124.9 127.5 14.7
123.7 126.2 127.0 15.1
122.6 125.3 126.8 15.1
Tolf b
172.9
1 b
Me2Sn:
5.0/7.5/10.2
175.0; Bu2Sn,
Cd: 13.5; Cg:
26.9/26.8; Cb:
27.9/27.5; Ca:
29.8/28.6
Bu2Sn, Cd:
13.5; Cg: 26.3;
Cb: 26.7;
620
2 b
114.6
112.0
148.4
132.4
116.7
133.6
113.7 140.9
131.6 135.6
123.0 125.4 126.9 15.1
)
194
3 b
148.3
133.4
117.2
134.6
113.7 140.7
131.0 135.6
122.2 125.3 126.8 14.9
201
Ca:25.8;
COOO: 177.3
a Spectrum recorded in DMSO-d6.
b Spectrum recorded in CDCl3, tolfenamic acid acid is poor soluble in CDCl3.

200
D. Ko6ala-Demertzi et al. / Journal of Organometallic Chemistry 620 (2001) 194–201
region of the tin-bound methyl groups, but integration
shows that in the case of the signal emerging at 1.15
ppm, two methyl groups are present indicating acciden-
tal equivalence. The most significant chemical shift
difference between the H spectra of the free drug and
1 is observed for the H5 atom.
3.2.3. Mo¨ssbauer spectra
Mo¨ssbauer spectra were obtained between 78 and 200
K for 1–3 and are reported in Table 4. The isomer shift
is correlated to the partial atomic charges (QSn) acting
on the Sn nucleus by means of the s-electron density; l
increases as QSn decreases. The increase in l with
increase of alkyl chain length follows the expected
pattern of +I inductive effect of the alkyl groups. The
fitting of the experimental data points by two symmetric
Lorentzian doublets for 1, shows the occurrence of two
distinct crystallographic enviroments around tin atoms.
From the quadrupole splitting value (QS) and the
point-charge approach, the relation QS=4[R] (1–
3 sin2 q cos2 q)1/2 gives an estimate of q, where 180°–2q
is the R–Sn–R bond angle [16b]. In the present com-
pound the bond angles calculated for the two tin sites
are 142° for the coordination with the high QS value
and 131° for low QS value. The presence of the two
different tin sites with almost equal spectral areas can
consequently propose for this compound the formula
[Me2LSnOSnLMe2]2. The values of the corresponding
hyperfine parameters are very similar to that already
reported for the adduct [(Me2SnOOCR)2O]2 (where
1
For 2, the appearance of two resonances for each of
NH, H3, H6 and CH3, in the ratio 1:3, shows the
existence of two inequivalent ligands in solution. The
NH, H3, H6 and H4 resonances associated with least
abundant ligand exhibit the greater shifts compared
with those found for the free drug. All shifts are
downfield except for the that due to H4 which is shifted
upfield by 0.16 ppm. Two resonances also appear for the
Ca,b,g atoms of the butyl group, with the Ca reso-
nances being separated by 73 Hz, the Cb by 24 Hz and
the Cg by 5 Hz. This result is expected as the more
remote the C nucleus is from the Sn centre, the less
susceptible it is to different Sn-atom environments.
Multiplicity of the butyl protons is also observed in
proton NMR spectrum as a result of their non-equiva-
lence [14]. In the 13C-NMR spectra, the greatest
downfield shift is exhibited by the C1 atom (4.7 ppm)
while the carbonyl C shifts downfield by 2.1 ppm. The
C5 resonance, by contrast, shifts upfield by 1.7 ppm.
The shifts of the benzoic ring proton resonances in 3
are similar to those observed in the other complexes.
The 13C-NMR spectrum reveals a small resonance
assignable to the CO2 nucleus and coordination is
confirmed by the fact that this resonance exhibits the
most important shift (4.4 ppm downfield). A downfield
shift is also observed for the C1 nucleus (2.1 ppm) while
smaller resonance shifts are found for the rest of the
R=m-CH3C6H4CHꢀCH and l=1.30, 1.13 mm s−1
;
DEQ=3.65, 3.14) [17b]. The spectra of 2 and 3 are each
characterized by a large quadrupole split doublet with a
relatively high isomer shift and a narrow linewidth. This
fact is indicative of pure compounds with a single Sn
site. At first inspection, the presence of a single quadru-
pole split resonance for 2 at all temperatures suggests
the equivalence in the environments about the two
crystallographically dissimilar Sn nuclei and reflects the
relative insensitivity of the i.s. and q.s to subtle changes
in atomic environment. The Mo¨ssbauer parameters for
2 are however very similar to those reported for the
adducts [ClR2SnOSnR2Cl]2 [16a]. A C–Sn–C bond an-
gle of 149° for 2 is calculated from the Mo¨ssbauer
analysis. The X-ray crystal structure for 2 indicates
C–Sn(1)–C and C–Sn(2)–C bond angles of 142.6(2)
and 132.6(2)° [145.6(3)° for minor component], respec-
tively. The infrared and NMR spectroscopy suggest a
distorted octahedral environment for 3, there
-
1
2
carbon atoms. The value of the J(Sn–Ca) and J(Sn–
Cb) coupling constants are 563.7 and 36.5 Hz, respec-
tively. Based on the coupling constants and according to
Holecˇek equation the C–Sn–C angle is estimated to be
131° [15]. An assignment of the structure for 3 can be
made based on literature data as similar values for
C–Sn–C angles have been determined (in CDCl3 solu-
tion) for hexacoordinated dibutyltin(IV) compounds for
which skewed-trapezoidal bipyramidal geometries were
found.
Table 4
Mo¨ssbauer effect spectral data at 80.0 K a
b
c
No.
l (mm s−1
)
DEQ (mm s−1
)
Y/2 (mm s−1
)
A
A
(×10−2) (K−1
)
[
(K)
C–Sn–C d (°)
D
1
1.37
1.00
1.33
1.34
3.58
3.21
3.34
3.32
0.38
0.40
0.39
0.40
48
52
100
100
−1.59
−1.60
−2.17
−2.17
106
106
91
142
131
2
3
149, 142.6(2) e, 132.6(2) e
149
91
a Estimated errors 92 in the last significant figures.
b Full width at half maximum.
c Slope of the best fit straight lines (−102 d ln A(T)/dT).
d Values calculated from Mo¨ssbauer spectra.
e Values from crystallographic data.

D. Ko6ala-Demertzi et al. / Journal of Organometallic Chemistry 620 (2001) 194–201
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octahedral or skew-trapezoidal bipyramidal
stereochemistry.
Variable temperature spectra were recorded for com-
plexes 1, 2 and 3 in order to extract molecular dynamics
information; the procedure has been previously de-
scribed [8b]. The plot of ln A(T) versus T gives a
straight line with slope −d ln A(T)/dT that character-
izes the tightness by which the tin atom is bounded into
the lattice. The experimental slope is −2.17×10−2
K−1 for both 2 and 3 with correlation coefficients r
better than −0.997. These values correspond to an
arrangement of noninteracting molecules in the solid
state for 2 and 3, and of interacting molecules by
hydrogen bonds or polymeric for 1 [17c]. The crystal
structure of 2 shows that C–H–p and p\p stacking
interactions are responsible for the value of −2.17×
10−2 K−1
.
4. Supplementary material
Crytallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic
Data Centre, CCDC, no. 149406 for compound 2.
Copies of this information may be obtained free of
charge from The Director, CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (Fax: +44-1223-336033;
e-mail deposit@ccdc.cam.ac.uk or www: http://
www.ccdc.cam.ac.uk).
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Walker, D. Stuart, Acta Crystallogr. Sect. A 39 (1983) 158. (c)
C.K. Johnson, ORTEP II, Report ORNL-5136, Oak Ridge Na-
tional Laboratory, Oak Ridge, TN, 1976.
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D.K.D. thanks ELPEN A.E. for the generous gift of
tolfenamic acid.
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